Glyphosate Summary of Analytical Chemistry and Residue Data DP#: 38 3931

page 1 of 13 UNITED STA

TES ENVIRONMENTA L PROTECTION AGENCY WASHINGTON, D.C. 20460 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION MEMORANDUM Date 24 - March - 201 1 S ubject : Glyphosate . Section 3 Registration for Application of the Potassium Salt of

Gly phosate to Roundup Ready ® Field Corn. Summary

of Analy tical Chemistry and Residue Data . PC Code s : 10361 3 and 417300 DP Barcode: D 38 3931 Decision No.: 4 37140 Registration No s . : 524 - 537; 524 - 5 49 Petition No .: 0 F 7741 Regulatory Action: Section 3 Risk Assessment Type: not applicable Case No.: 178 T XR No.: not applicable CAS No.: 70901 - 20 - 1 MRID No.: 47 982201 40 CFR: 180 .364 F rom : Tom Bloem, Chemist

Risk Assessment Branch 1; Health Effects Division (RAB1/HED; 7509P) T hrough : George F. Kramer, Ph.D., Senior Chemist

RAB1/HED (7509P) T o : James Tompkins/Hope Johnson RM 25

Registration Division (RD; 7505P) Monsanto indicated that they have develop ed a new Roundup Ready ® trait for field corn which enables properly

timed gly

phosate ( N - (phosphonomethyl)glycine) appl ications to provide tassel control ; Monsanto indicated that tassel control is desired as this wil l allow the generation of specific cross pollinations without the us e of traditional methods to contro l self pollination . This new Roundup Ready ® trait will be used only

in seed corn production and Monsanto te rmed the process Round Hy

bridization SystemTM ( RHS TM ). The generation of RHS TM seed corn involves slightly later application timings than th ose currently registered.Glyphosate Summary of Analytical Chemistry and Residue Data DP#: 38 3931

page 2 of 13 Executive Summary Background: Gly

phosate is a nonselective Group 9 herbicide which disrupts the sy nthesis of the aromatic amino acids ty

rosine, try

ptophan, and phenylalanine through inhibition of 5 - enolpy ruvylshikimate - 3 - phosphate sy nthase (EPSPS). Gly

phosate is currently

registered for pre and post - emergence application to a variety of fruit, vegetable, and field crops. Tolerances are currently established for residues of gly phosate in/on various plant commodities (including field corn) at 0.2 - 400 ppm (40 CFR §180.364(a)) and for the combined residues of gly phosate and N

acetyl - gly phosate (expressed as gly phosate) in/on field corn, soy bean, aspirated grain fractions (AGF ) , and livestock commodities at 0.1 - 310 ppm. The Gly phosate Reregistration Eligibility Decision (RED) document was issued September 1993 . A Registration Review Scoping document was completed in 20 09 (D362745, J. L angsdale et al ., 3 - Jun - 2009). The petitioner proposed a Section 3 registration for application of gly phosate to field corn used in RHS TM seed corn production. The petitioner is also proposing a tolerance for residues of gly phosate only in/on field corn forage of 1 3 ppm (revisions to the currently- established field corn stover and grain tolerances are not requested) . Tolerances for the combined residues of gly phosate and N

- acetyl - gly

phosate (expressed as gly phosate ; see Attachment 1 for structures) in/on field corn forage, stover, and grain are currently established at 6.0 ppm, 100 ppm, and 5.0 ppm, respectively

(180.364(a)(2)). HED notes that the tolerance expression includes residues of N - acetyl - gly

phosate due to the introduction the Optimum  GAT  field corn variety (see Nature of the Residue Section in the Executive Summary for a description of this variety ). Proposed Use: The petitioner submitted proposed supplemental labels for Roundup WeatherMAX ® (EPA Reg. No. 524 - 537) and Roundup Power MAX ® (Reg. No. 524 - 549); both of these products are soluble - concentrate ( SC ) formulations consisting of gly phosate as the potassium salt at 4.51 lb ae/gallon. The submitted supplemental labels indicate that the application s cenarios are for use in research field trials and for seed production of corn hy brids using the RHS TM s ys tem . Table 3 is a summary of the proposed application scenarios. The proposed use directions are similar to that currently registered with the excepti on of the tassel control instructions (V8 - V13); the maximum seasonal application rate is the same. HED requests that the supplemental labels be altered to indicate the following (a revised Section B is requested): ( 1 ) the minimum spray volume for ground and aerial application is >2 gallons per acre ( GPA ) ; ( 2 ) postemergent directions should indicate that they apply to field corn up to the V8 crop stage and that a maximum of 2.3 lb ae/acre/season may be applied; and ( 3 ) preharvest interval (PHI) of 30 days for forage and 7 days for grain and stover. Nature of the Residue – P rimary Crops : Metabolism studies conducted with nontransgenic corn, cotton, soy

beans, and wheat were previously submitted and reviewed . Based on these data, HED concluded that the residue of concern in nontransgenic plants is gly phosate (Memo, R. Perfetti, 19 - Oct - 1992; RED, R. Perfetti, 27 - Oct - 1992; Memo, R. Perfetti, 17 - Mar - 1994). Metabolism studies have also been submitted on gly phos ate - tolerant canola (D242628, T. Bloem, 30 -Nov - 1998) and gly

phosate - tolerant field corn ( Roundup Ready ® field corn ; D217539, G. Kramer, 14 - Mar - 1996). The gly phosate - tolerant canola and field corn were genetically modified to express the EPSPS gene derived from Agrobacterium sp. ( strain CP4 ) which codes for an EPSPS protein that has reduced affinity for gly phosate as compared to the endogenous EPSPS protein. The gly

phosate - tolerant canola and corn were also genetically engineered to express theGlyphosate Summary of Analytical Chemistry and Residue Data DP#: 38 3931

page 3 of 13 oxireductas e gene which convert s gly phosate to the nonherbicidal AMPA (aminomethyl phosphonic acid) . Metabolism in these varieties of transgenic canola and corn was essentially the same as th e nontransgenic plants. Th erefore , it was concluded that the terminal res i due to be regulated, in nontransgenic plants and transgenic field corn and canola modified to express the Agrobacterium sp. EPSPS and oxireductase genes, is gly phosate. Subsequent to this decision, HED approved DuPont request s permitting the commercialization of Optimum  GAT  soy

bean and Optimum  GAT  field corn (D346713, T. Bloem, 12 - Mar 2008; D357880, T. Bloem, 29 - Oct - 2008; D361315, T. Bloem, 14 - Jan - 2010) . Optimum  GAT  soy

bean was engineered to express the gat 4601 gene ( derived from Bacillus licheniformis ; soil bacterium) and Optimum  GAT  field corn was engineered to express the gat 4621 gene ( derived from Bacillus licheniformis ; soil bacterium) and the zm - hra gene (modified version of maize acetolactate sy nthase (ALS) gene) . The gat 4601 and the gat

4621 genes confer tolerance to gly phosate via acetylation of the secondary amine group of gly

phosate (results in formation of the nonherbicidal N - acetyl - gly

phosate) ; the zm - hra gene in Optimum GAT  field corn, encodes for an ALS protein which is not sensitive to the AL S - inhibiting herbicides . As a result of the introduction of th e s e seed line s , HED concluded that the residues of concern in plants for tolerance expression and risk assessment should change from gly phosate to the combined residues of gly phosate and N

- acetyl - gly

phosate (D346713, T. Bloem, 12 - Mar 2008). Subsequent to this decision, it was determined that only the tolerance expression for field corn and soy

bean would change from gly phosate to the combined residues of gly phosate and N

acetyl - gly phosate; the tolerance expression for all other crops would remain as gly phosate. The current action is requesting application of gly phosate to a new variety

of genetically

altered corn developed by

Monsanto ( MON 87427 and MON87441) . Monsanto indicated that MON 87427 and MON87441 are tolerant to gly phosate via insertion of the CP4 EPSPS (5 - enolpy ruvylshikimate - 3 - phosphate sy nthase) gene which, as indicated above, encodes for an EPSPS protein whic h is not inhibited by gly phosate. MON 87427 and MON 87441 were also genetically

altered to utilize a promoter and intron combination to limit expression of CP4 EPSPS in pollen microspore and tapetum cells. Therefore, little to no CP4 EPSPS protein is exp ressed in MON 87427 and MON87441 pollen, thus pollen from these events is susceptible to gly phosate. Gly

phosate application to MON 87427 and MON87441 at early tassel development allows specific cross pollinations to be made without using the traditional m ethods to control self pollination. The petitioner indicated that the resulting hy brid corn seed has full vegetative and reproductive tolerance to gly phosate due to the dominance of the gly phosate - tolerant trait inherited from the male parent. A metaboli sm study has been previously

been conducted with field corn genetically

altered to express CP4 EPSPS with HED concluding that the residue of concern was gly

phosate (see above) . HED concludes that these data and decisions are translatable to MON 87427 and MON87441 . Nature of the Residue – Livestock: The qualitative nature of the residue in livestock following dosing with gly

phosate and AMPA is adequately understood. Studies with lactating goats and laying hens fed a mixture of gly phosate and AMPA indi cate that the primary route of elimination was by excretion (urine and feces). HED determined that the terminal residue to be regulated in livestock is gly

phosate (Memo, R. Perfetti, 19 - Oct - 1992; RED, R. Perfetti, 27 - Oct - 1992; Memo, R. Perfetti , 17 - Mar - 1994).Glyphosate Summary of Analytical Chemistry and Residue Data DP#: 38 3931

page 4 of 13 Since the Optimum  GAT  soy bean and field corn metabolism studies resulted in significant residues of N

- acetyl - gly

phosate, DuPont submitted summaries of in vitro (rumen fluid, fertile hen egg, and rat liver S9 supernatant) and in vivo (rat metabolism study ) studies conducted with the N - acetyl - gly

phosate metabolite and submitted goat and hen metabolism studies conducted with the N - acetyl - gly

phosate metabolite . Based on these data and the gly phosate metabolism studies , HED concluded that the residues of concern in livestock following consumption of gly phosate and N - acetyl - gly

phosate , for tolerance expression and risk assessment purposes, are gly phosate and N - acetyl - gly

phosate (D346713, T. Bloem, 12 - Mar - 2008; D361315, T. Bloem, 14 - Jan - 201 0) . Based on these data and since MON 87427 and MON87441 field corn do not result in any addition metabolites, HED concludes that the previous decisions concerning the residues of concern in livestock remain appropriate. Magnitude of the Residue – Field Corn : The petitioner submitted 10 field corn field trials conducted in the North American Free Trade Agreement (NAFTA ) growing zones 5 (n=8) and 5A (n=2). Each field trial consisted of two treated plots planted with inbred NK603 (tolerant to gly phosate vie insertion of the CP4 EPSPS gene) as the male pollen donator and either inbred MON 87427 or MON 87441 as the female parent (see Nature of the Residue section in the Executive Summary

for a description of these varieties). P rovided a revised Sec tion B is submitted as described above, the employed application scenarios adequately mimic the proposed application scenario. The harvested field corn forage, stover, and grain samples were analy zed for residues of gly

phosate and AMPA using an adequately- validated method (storage interval has also been validated). The maximum gly phosate residue in the treated field corn forage, grain and stover samples were 9.19 ppm, 0.80 ppm, and 30.85 ppm, respectively . HED has previously determined that gly

phosate residues do not concentrate in corn processed commodities (D216229, W. Cutchin, 21 - Mar - 1996). Since the maximum gly

phosate residue in field corn stover and grain i s signif icantly less than the currently- established tolerances, revisio n of the stover and grain tolerances is unnecessary . However, the maximum gly phosate residue in field corn forage is greater than the currentlyestablished tolerance. HED entered the gly phosate field corn forage residue data into the Agency ’s tolerance spreadsheet as specified by the Guidance for Setting Pesticide Tolerances Based on Field Trial Data ; the resulting recommended tolerance is 13 ppm. Since the petitioner proposed field corn forage tolerance is for residue of gly phosate only, HED requests that a revised Section F be submitted proposing 13 - ppm field corn forage tolerance for the combined residues of gly

phosate and N

- acetyl - gly

phosate (expressed as gly phosate) . HED notes that only

10 field trials were conducted and only in NAFTA growing zone 5. Therefore, the petitioner has not fulfilled the geographical requirements suggested in OPPTS 860.1500 for a field corn registration. The petitioner noted that trials were only conducted in Zone 5 as this is the major hy brid seed cor

n production region in the U.S. Based on this and since residues in stover and grain were significantly lower than the currently- established tolerance and since the currently established 400 ppm nongrass animal feed and 300 ppm grass forage tolerances are significantly greater than the HED - recommend field corn forage tolerance, meaning that residues in field corn forage will not effect the currently- established ruminant tolerances, additional field trial data are not required.Glyphosate Summary of Analytical Chemistry and Residue Data DP#: 38 3931

page 5 of 13 Magnitude of the Residue - Livestock: The revised OPPTS 860.1000 Table 1 (J. Stokes; Jun 2008) indicates that field corn forage (roughage), stover (roughage), grain (carbohydrate concentrate), and milled by products (carbohydrate concentrate) may fed to dairy

/beef cattle and grain and milled by

products may

be feed to poultry

and hogs. Since the current petition requires a revision to only

the field corn forage tolerance (tolerance increased from 6.0 ppm to 13 ppm) and since the roughage portion of the beef/dairy cattle diet will b e occupied by the currently

established 400 ppm nongrass animal feed and 300 ppm grass forage tolerance s , HED concludes that the currently- established livestock tolerances remain appropriate. Nature/ Magnitude of the Residue - Rotational Crops : Based on a previously- reviewed confined rotational crop studies ( 3.71 lb ae/acre; MRIDs 41543201 and 41543202, A. Abramovitch, 14 - Oct - 1992 ) which resulted in gly phosate residues of >0.01 ppm in barley grain only (0.018 ppm; 125 - day plantback interval ( PBI) ) and th e limit of quantitation ( LOQ ) for the tolerance enforcement method of 0.05 ppm, HED concluded that a 30 - day PBIwas appropriate for all nonlabeled crops (D200041, G. Kramer, 12 - May- 1994; field rotational crop study has not been submitted) . HED notes that the rate employed in the confined rotational crop study was 0.6x the proposed rate; however, bas ed on the L OQ for the tolerance - enforcement method and since confined rotational crop study employed application to bare soil, HED concludes that the proposed 3 0 - day

PBIfor all crops is acceptable. Analytical Enforcement Method: The field corn forage, stover, and grain samples collected from the crop field trials submitted in support of the current petition were analy zed for residues of gly phosate using a method similar to the current enforcement method. Based on this similarity and since the field trial study resulted in acceptable recoveries, HED concludes that the current enforcement method is adequate to enforce the tolerances associated with t he current petition. Recommendations: Provided the petitioner submits a revised Section s B and F (see below), HED concludes that the residue chemistry database supports an unconditional registration for the proposed application scenario . A human - health risk assessment will be prepared as a separate document. Summary of Residue Chemistries Deficiencies: ●Section B : HED requests that the supplemental labels be altered to indicate the following: (1) the minimum spray

volume for ground and aerial app lication is >2 GPA; ( 2 ) postemergent directions should indicate that they apply to field corn up to the V8 crop stage and that a maximum of 2.3 lb ae/acre/season may be applied; and ( 3 ) PHI of 30 days for forage and 7 days for grain and stover. ●Section F: HED requests that a revised Section F be submitted proposing a 13 - ppm field corn forage tolerance for the combined residues of gly phosate and N

- acetyl - gly

phosate (expressed as gly phosate).Glyphosate Summary of Analytical Chemistry and Residue Data DP#: 38 3931

page 6 of 13 Background Gly phosate is a nonselective Group 9 herbicide which disrupts the sy nthesis of the aromatic amino acids ty

rosine, try

ptophan, and phenylalanine through inhibition of EPSPS. Gly phosate is currently registered for pre - and post - emergence application to a variety of fruit, vegetable, and field crops. To lerances are currently established for residues of gly phosate in/on various plant commodities (including field corn) at 0.2 - 400 ppm (40 CFR §180.364(a)) and for the combined residues of gly

phosate and N

- acetyl - gly

phosate (expressed as gly phosate) in/on fie ld corn, soy bean, AGF, and livestock commodities at 0. 1 - 310 ppm. The Gly phosate RED document was issued September 1993. A Registration Review Scoping document was completed in 2009 (D362745, J. L angsdale et al ., 3 - Jun - 2009). The chemical structure/nomen clature physicochemical propertie s of gly phosate are presented in Tables 1 and 2 . T able 1 : Glyphosate Nom enclature. Compound P O O H O H N H O H O

Common name Glyphosate (PC code 471300) Company experimental name DPX - B2856 IUPAC /CAS name N - (phosphonomethyl)glycine CAS registry number 1071 - 83 - 6 T able 2 : Physicochemical Properties of Technical Grade Glyphosate. Melting point 189.5 ± 0.5 °C The Pesticide Manual, 13 th Edition pH 1.9 at 20 °C Density 1.705 g/cm3 at 20 °C Water solubility 10.5 g/L at 20 °C Solvent solubility acetone 0.078 g/L methanol 0.231 g/L hexane 0.026 g/L ethyl acetate 0.012 g/L dichloromethane 0.233 g/L n - octanol 0.020 g/L propan - 2 - ol 0.020 g/L toluene 0.036 g/L European Commission: Glyphosate 6511/VI/99 - final, 1/21/02 Vapor pressure 1.31 x 10 - 2 mP a at 25 °C The Pesticide Manual, 13 th Edition Dissociation constant, pKa 0.8 (1 st phosphoric), 2.3 (carboxylate), 6.0 (2 nd phosphoric), and 11.0 (amine) Knuuttila. 1979 Acta Chem. Scand. B 33:623 - 626 Octanol/water partition coefficient, Log(KOW) - 3.2 (pH 2 - 5, 25 °C ) European Commission: Glyphosate 6511/VI/99 - final, 1/21/02 UV/visible absorption spectrum ε = 0.086 (295nm)Glyphosate Summary of Analytical Chemistry and Residue Data DP#: 38 3931

page 7 of 13 860.1200 Directions for Use The petitioner submitted proposed supplemental labels for Roundup WeatherMAX ® (EPA Reg. No. 524 - 537) and Roundup Power MAX ® (Reg. No. 524 - 549); both of these products are SC formulations consisting of gly phosate as the potassium salt at 4.51 lb ae/gallon . The submitted supplemental labels indicate that the application scenarios are for use in research field trials and for seed production of corn hy brids using the RHS TM system. Table 3 is a summary of the proposed application scenarios. The proposed use directions are similar to that currently registered with the exception of the tassel control instructions (V8 - V13); maximum seasonal application rate is the same. HED requests that the supplemental label s be altered to indicate the following (a revised Section B is requested) : (1) the minimum spray volume for ground and aerial application is >2 GPA; ( 2 ) postemergent directions should indicate that they apply to fi e ld corn up to the V8 crop stage and that a maximum of 2. 3 lb ae/acre/season may be applied; and ( 3 ) PHI of 30 days for forage and 7 days for grain and stover . Table 3 : Summary of Proposed Roundup Ready® Field Corn Application Scenario . Formulation (EPA Reg. No.) App. Timing App. Rate (lb ae/acre) Max. App. Rate

(lb ae/acre) Use Directions and Limitations Roundup WeatherMAX ® (EPA Reg. No. 524 - 537 ; SC; 4.51 lb ae/gal ) Roundup Power MAX ® ( EPA Reg. No. 524 - 549 ; SC; 4.51 lb ae/gal ) preplant, at planting, preemergence not specified 3.72

- For use in research field trails and for seed production of corn hybrids using RHS TM

.

- Allow a minimum of 10 days between postemergent applications. postemergence 0.56 - 0.78 not specified tassel control (V8 - V13 or 100 growing degree units; before flowering) 0.39 - 1.13 2.26 preharvest 0.78 not specified postharvest not specified not specified maximum seasonal application rate -- 5.98 860.1300 Nature of the Residue - Plants and Livestock See Executive Summary . 860.1340 Residue Analytical Methods The field corn forage, stover, and grain s amples collected from the crop field trials submitted in support of the current petition were analy zed for residues of gly

phosate and AMPA usi ng an adequately- validated high - performance liquid chromatography ( HPL C ) equipped with a fluorescence detector method. Briefly, samples were extracted with chloroform:aqueous 0.1 N HCl (1:3). The aqueous layer was collected and applied to a Chelex® 100 column eluted with 6 N HCl followed by

an anion exchange resin also eluted with 6 N HCl. The sample was concentrated, di ssolved in water, and analy zed. Based on the lowest level of method validation ( LLM V ) , the L OQ is 0.05 ppm for each analy te/matrix. Apparent residues of gly phosate and AMPA were <LOQ in all control samples. Based on the acceptable recoveries and since i nterfering residues were <LOQ in controls, the employed analy ti cal method is adequate for data collection purposes. The data - collection method is similar to the current enforcement method (Memo, R. Perfetti, 10/27/92). Based on this similarity and sinc e acceptable recoveries were attained in the field trials, HED concludes that the current enforcement method is adequate to enforce the tolerances associated with the current petition.Glyphosate Summary of Analytical Chemistry and Residue Data DP#: 38 3931

page 8 of 13 860.1360 Food and Drug Administration (FDA) Multiresidue Methods (M RMs) Protocols The Pestrak database (1990) indicate s that recoveries are not likely for gly phosate under FDA Multiresidue Methods. No further data regarding multiresidue methods are required for this proposed use. 860.1380 Storage Stability The maximum interval from collection to extraction for the forage, stover, and grain samples w as 284 days (9.5 months). Previously submitted data indicate that g ly phosate is stable for 31 months in/on fortified and frozen corn, sorghum straw, clover, tomato, and soy bean forage; residues of AMPA fluctuated from 50 - 99% in the same time period (D206278, C. Eiden, 17 - Nov - 1994). Since AMPA is not a residue of concern in plants (Memo, R. Perfetti , 17 - Mar 1 994 ) , HED concludes that the available storage stability data are sufficient to validate the residue data submitted in support of the current petition. 860.1480 Meat, Milk, Poultry, and Eggs The revised OPPTS 860.1000 Table 1 (J. Stokes; Jun - 2008) indicates that field corn forage (roughage), stover (roughage) , grain (carbohydrate concentrate), and milled by products (carbohydrate concentrate) may fed to dairy

/beef cattle and grain and milled by products may

be feed to poultry

and hogs. Since the current petition requires a revision to only the field corn forage tolerance (tolerance increased from 6.0 ppm to 13 ppm) and since the roughage portion of the beef/dairy

cattle diet will be occupied by the currently established 400 ppm nongrass animal feed and 300 ppm grass forage tolerances, HED concludes that the currently- established livestock tolerances remain appropriate. 860.1500 Crop Field Trials 4 7 982201 .der.doc The petitioner submitted 10 fi eld corn field trials conducted in the NAFTA growing zones 5 (n=8) and 5A (n=2). Each field trial consisted of two treated plots planted with inbred NK603 (tolerant to gly

phosate vie insertion of the CP4 EPSPS gene) as the male pollen donator and either i nbred MON 87427 or MON 87441 as the female parent (see Nature of the Residue section in the Executive Summary for a description of these varieties) . Table 4 is a summary of the employed application scenarios; provided a revised Section B is submitted as described above, the employed application scenarios adequately mimic the pro posed application scenario . All applications were broadcast sprays made with Roundup WeatherMAX ® (EPA Reg. No. 524 - 537; water - soluble concentrate formulation of gly phosate formulated as the potassium salt (4.5 lb ae/gal; 540 g ae/l)) and included (NH 4 ) 2 SO 4 and a nonionic surfactant (NI S). The harvested field corn forage, stover, and grain samples were analy zed for residues of gly

phosate and AMPA (aminomethyl phosphonic acid) using an adequately- validated method (storage interval has also been validated). Table 5 is a summary of the residue data. Ingeneral, residues were higher under the treatment 2 application scenario as compared to the treatment 3 application scenario (only sl ightly higher in grain).Glyphosate Summary of Analytical Chemistry and Residue Data DP#: 38 3931

page 9 of 13 Conclusions: Tolerances for the combined residues of gly phosate and N

- acetyl - gly

phosate (expressed as gly

phosate ) in/on field corn forage, stover, and grain are currently established at 6.0 ppm, 100 ppm, and 5.0 ppm, respective ly (180.364(a)(2)). HED notes that the tolerance expression includes residues of N - acetyl - gly

phosate due to the introduction the Optimum  GAT  field corn variety ( see Nature of the Residue Section in the Executive Summary for a description of this variety ) . Since the maximum gly

phosate residue in field corn stover (30.85 ppm) and grain (0.80 ppm) i s signif icantly less than the currently- established tolerances , revision of the stover and grain tolerances is unnec essary . However, the maximum gly phosate residue in field corn forage (9.19 ppm) is greater than the currently- established tolerance. HED entered the gly phosate field corn forage residue data from the treatment 2 scenario (resulted in higher residues) int o the Agency ’s tolerance spreadsheet as specified by the Guidance for Setting Pesticide Tolerances Based on Field Trial Data (see attachment 2); the resulting recommended tolerance i s 13 ppm (see Attachment 3) . Since the petitioner proposed field corn forage tolerance is for residue of gly phosate only, HED requests that a revised Section F be submitted proposing a 13 - ppm field corn forage tolerance for the combined residues of gly phosate and N

- acetyl - gly

phosate . HED notes that only

10 field trials were conducted and o nly in NAFTA growing zone 5. Therefore, the petitioner has not fulfilled the geographical requirements suggested in OPPTS 860.1500 for a field corn registration (zones 1 (n=1), 2 (n=2), 5 (n=17), and 6 (n=1)). The petitioner noted that trials were only conducted in Zone 5 as this is the major hy brid seed corn production region in the U.S. Based on this and since residues in stover and grain were significantly

lower than the currently- established to l erance and since the currently established 400 ppm nongrass animal feed and 300 ppm grass forage tolerances are significantly greater than the HED - recommend field corn forage tolerance, meaning that residues in field corn forage will not a ffect the currently- established ruminant tolerances, additional field trial data are not requi red. Table 4 : Summary of Application Scenarios. lb ae/acre (kg ae/ha)

premeergence V3 - V4 V7 - V8 V9 - V10 V12 - V13 late dent total treatment 2 0.76 - 0.80

(0.85 - 0.90) 1.09 - 1.15

(1.22 - 1.29) 1.09 - 1.15

(1.22 - 1.29) 1.0 - 1.17

(1.20 - 1.31) 1.12 - 1.15

(1.26 - 1.29) 0.77 - 0.81

(0.86 - 0.91) 6.00 - 6.15

(6.73 - 6.89) treatment 3 1.54 - 1.58

(1.73 - 1.77) 1.12 - 1.16

(1.26 - 1.30) 1.10 - 1.15

(1.23 - 1.29) 0.77 - 0.80

(0.86 - 0.90) 0.77 - 0.80

(0.86 - 0.90) 0.77 - 0.81

(0.86 - 0.91) 6.14 - 6.23

(6.86 - 6.98) retreatment interval (RTI; days) -- 16 - 35 9 - 25 6 - 11 4 - 11 55 - 88 -- Table 5: Summary of Glyphosate and AMPA Residues. Analyte Commodity Treatment Residues (ppm) Range Mean glyphosate forage 2 2.59 - 9.19 5.73 3 1.95 - 6.88 4.34 stover 2 11.08 - 30.85 18.05 3 4.26 - 21.47 12.42 grain (collected 1 day prior to the final application) 2 0.19 - 0.77 0.40 3 0.15 - 0.45 0.26 grain (collected 7 days after the final application) 2 0.19 - 0.80 0.46 3 0.16 - 0.74 0.34Glyphosate Summary of Analytical Chemistry and Residue Data DP#: 38 3931

page 10 of 13 Table 5: Summary of Glyphosate and AMPA Residues. Analyte Commodity Treatment Residues (ppm) Range Mean

AMPA forage 2 0.07 - 0.25 0.15 3 0.07 - 0.19 0.12 stover 2 0.14 - 0.41 0.28 3 0.07 - 0.34 0.21 grain (collected 1 day prior to the final application) 2 0.05 - 0.11 0.08 3 <0.05 - 0.08 0.06 grain (collected 7 days after the final application) 2 0.06 - 0.10 0.08 3 <0.05 - 0.08 0.06 860.1520 Processed Food and Feed HED has previously

determined that gly

phosate residues do not concentrate in corn processed commodities (D216229, W. Cutchin, 21 - Mar - 1996). 860.1850 & 860.1900 Confined and Field Accumulation in Rotational Crops Based on a previously- reviewed confined rotational crop studies ( 3.71 lb ae/acre; MRIDs 41543201 and 41543202, A. Abramovitch, 14 - Oct - 1992 ) which resulted in gly phosate residues of > 0.01 ppm in barley

grain only

(0.018 ppm; 125 - day

PBI) and the LOQ for the tolerance enforcement method of 0.05 ppm, HED concluded that a 30 - day PBIwas appropriate for all nonlabeled crops (D200041, G. Kramer, 12 - May- 1994; field rotational crop study has not been submitted) . HED notes that the rate employed in the confined rotational crop study was 0.6x the proposed rate; however, bas ed on the L OQ for the tolerance - enforcement method and since confined rotational crop study employed application to bare so il , HED concludes that the a 30 - day PBIfor all nonlabeled crops is acceptable. 860.1550 Proposed Tolerances Table 6 is a summary

the proposed and HED - recommend ed tolerances for the combined residues o f gly phosate and N

- acetyl - gly

phosate (expressed as gly phosate) ; a revised Section F is requested. There are no Mexican, Canadian, or Codex field corn forage maximum residue limits (MRL s) but there is a Canadian MRL in/ on “corn” of 3.0 ppm and a Codex MRL s in/ on “maize ” of 5 ppm which could be applied t o any corn commodity (see Attachment 1) . Regardless, since the residue s of concern differ, harmonization is not possible. Table 6 . Tolerance Sum ma ry . Commodity Proposed

Tolerance (ppm) HED - Recommended

Tolerance (ppm) Comments

c orn, field , forage 13 13 The petitioner proposed tolerance is for residues of glyphosate only while the HED - recommended tolerance is for the combined residues of glyphosate and N - acetyl glyphosate; a revised Section F is requested . Attachment 1 - International Residue Limit Status sheet Attachment 2 - Chemical Name and Structure Table Attachment 3 - Tolerance Spreadsheet Summary RDI: RAB1 Chemists ( 8 - Dec - 20 10 ) T. Bloem:S10945:Potomac Yard 1:703 - 605 - 0217:7509P:RAB1Glyphosate Summary of Analytical Chemistry and Residue Data DP#: 38 3931

page 11 of 13 Attachment 1 – Glyphosate International Residue Limit Status S heet Summary of US and International Tolerances and Maximum Residue Limits Residue Definition :

US Canada Mexico 2 Codex 40 CFR 180.364(a)(2): glyphosate and N - acetyl - glyphosate N - (phosphonomethyl) glycine , including the metabolite aminomethyl phosphonic acid -- glyphosate Tolerance (ppm) /Maximum Residue Limit (mg/kg) Commodity 1 US Canada Mexico 2 Codex Corn, field, forage 13 3.0 (corn) -- 5 (maize) Completed M. Negussie; 12/01/2010 1 Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and not those proposed by the applicant. 2 M exico adopts US tolerances and/or Codex MRLs for its export purposes.Glyphosate Summary of Analytical Chemistry and Residue Data DP#: 38 3931

page 12 of 13 Attachment 2 - Chemical Structures

C o mp ound S tructure Glyphosate N - (phosphonomethyl)glycine P O O H O H N H O H O

N - a cetyl - glyphosate N - acetyl -N - (phosphonomethyl)glycine AMPA (aminomethyl)phosphonic acid P O O H O H N H 2 N - a cetyl - AMPA [(acetylamino)methyl]phosphonic acid P O O H O H N H C H 3 O P

O O H O H N O H O O

C H 3Glyphosate Summary of Analytical Chemistry and Residue Data DP#: 38 3931

page 13 of 13 Attachment 3 : Tolerance Spreadsheet Summary

Regulator: EPA Chemical: glyphosate Crop: field corn forage PHI: App. Rate: Submitter:

n: 22 min: 2.59 max: 9.19 median: 5.37 average: 5.73 95th Percentile 99th Percentile 99.9th Percentile 9.0 11 12 (11) (13) (--) 10 13 17 (13) (18) (--) 15 12 30 0.9669 p-value > 0.05 : Do not reject lognormality assumption Approximate Shapiro-Francia Normality Test EU Method I Normal

UCLMedian95th 95/99 Rule EU Method II Distribution-Free Mean+3SD